Search PubMed⌕ Search

Biomedical subjects

D M Cummings

Publications and source records attributed to D M Cummings.

At least 37 records · Page 2Linked to original sources
PubMed1993

Disposition of digoxin immune Fab in patients with kidney failure.

Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free digoxin were studied in five digoxin-toxic patients with end-stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (+/- SD) serum creatinine of 5.9 +/- 1.2 mg/dl (four patients were receiving long-term hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration-time profile of Fab appeared to be similar to the concentration-time profile of total digoxin. The mean (+/- SD) half-lives of the alpha and beta disposition phases of Fab were 13 +/- 5 hours and 96 +/- 31 hours, respectively, which were similar to the alpha and beta parameter estimates of total digoxin (14 +/- 4 and 123 +/- 16 hours, respectively). Steady-state volume of distribution and systemic clearance of Fab were 0.29 +/- 0.11 L/kg and 0.057 +/- 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total digoxin are markedly delayed in patients with end-stage renal disease, which may necessitate prolonged clinical monitoring.

Aged↗
PubMed1993

Nonsteroidal anti-inflammatory drugs. Tailoring therapy to achieve results and avoid toxicity.

When used appropriately, non-steroidal anti-inflammatory drugs (NSAIDs) are safe and effective for treating pain and inflammation. NSAIDs that block both the lipoxygenase and cyclooxygenase pathways may be advantageous in some patients. New classes of NSAIDs that may have a more favorable safety profile than older agents may improve patient outcome. However, all patients receiving NSAIDs, especially the elderly, should be carefully monitored for possible drug-related complications.

Absorption↗
PubMed1992

Lack of effect of pentoxifylline on red blood cell deformability.

The proposed mechanism of action for pentoxifylline's beneficial effect in peripheral vascular disease is an improvement in red blood cell deformability. Likewise, single doses of pentoxifylline in healthy volunteers have been shown to improve whole blood filterability, which was suggested to occur as a result of augmented red blood cell deformability. To further assess this, the authors studied the effects of short-term pentoxifylline administration (400 mg three times daily for 7 days) on red blood cell deformability in ten healthy, methylxanthine-free, nonsmoking volunteers. Blood samples were obtained at baseline and after 1 week of therapy (steady-state). Samples were analyzed for red blood cell deformability by ektacytometry, which showed no significant change in deformability in any subject. Despite the improvement in whole blood filterability associated with both single-dose and short-term administration of pentoxifylline, the current study demonstrates no effect on red blood cell deformability after short-term administration in healthy volunteers.

Adult↗
PubMed1992

Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies.

Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration-time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy.

Adult↗
PubMed1991

Monitoring serum digoxin concentrations during digoxin immune Fab therapy.

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Adult↗
PubMed1991

The role of calcium channel blockers in the treatment of essential hypertension.

Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.

Animals↗
PubMed1990

Clinical pharmacology and therapeutics in primary care: an elective for fourth-year medical students.

A 1-month elective course in clinical pharmacology in primary care has been developed and is offered six times a year for fourth-year medical students. The major course objective is to teach the student to apply the principles of rational therapeutics in the routine practice of primary care. The faculty includes clinical pharmacists and primary care physicians from the Department of Family Medicine. Two students each month rotate through a combined didactic and experiential curriculum oriented toward the rational selection and monitoring of drugs in inpatient and outpatient settings. Students interact daily with faculty members and have ample opportunity to evaluate drug therapy regimens and assist in designing new therapeutic strategies. Students are evaluated on their performance in conferences, written consultations, and oral case challenges. Evaluations by students indicate that this elective is a valuable educational experience.

Curriculum↗
PubMed1990

ACE inhibitors. A safe option for hypertension and congestive heart failure.

The Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has recently recommended angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and diuretics as potential first-step agents for the pharmacologic treatment of hypertension. ACE inhibitors should be considered an important option in most patients because of their safety profile, absence of adverse metabolic effects, and positive cardiac and renal effects. If the response to an ACE inhibitor is inadequate, a diuretic or another agent can be added, and this combination should be effective and well tolerated in 85% to 90% of patients. ACE inhibitors can be used to treat congestive heart failure and to prevent the renal complications of hypertension and diabetes mellitus, significantly expanding their use in patients with these high-risk conditions. They also can be used concurrently with other antihypertensive agents, digitalis, cardiac glycosides, and lithium and are not contraindicated in most of the diseases commonly seen in hypertensive patients.

Aged↗
PubMed1990

Effect of digoxin Fab antibodies on five digoxin immunoassays.

Following digoxin Fab antibody (FAB) administration in digitalis-toxic patients, total serum digoxin concentrations (SDCS) become elevated, but do not correlate with pharmacologic activity. In an attempt to accurately measure free (pharmacologically active) SDC in the presence of FAB, we assessed the utility of five digoxin immunoassays: fluorescence polarization immunoassay (FPIA), ultrafiltration with FPIA (ULTRA-FPIA), enzyme multiplied immunoassay (EMIT), radioimmunoassay (RIA), and American Dade's STRATUS (STRATUS). To normal human serum samples containing 2 and 4 ng/ml of digoxin, FAB was added in escalating quantities of 0-1.9 micrograms. In addition, 1.9 micrograms of FAB was added to two serum samples containing no digoxin. SDCS reported by FPIA for each 2 ng/ml samples, in order of ascending FAB doses, were 2.08, 1.94, 2.02, 1.99, 1.95, and 1.93 ng/ml, while the SDCS from the ULTRA-FPIA were 2.00, 1.76, 1.56, 1.36, 1.16, and 0.98 ng/ml. Results similar to the ULTRA-FPIA were obtained with the STRATUS, RIA, and EMIT, although the SDCS from the EMIT (p less than 0.05) samples exhibited greater fluctuation. The 4 ng/ml samples demonstrated similar patterns among the assays although no statistical differences were noticed between EMIT and ULTRA-FPIA. Samples containing FAB without digoxin only adversely affected the RIA, which reported mean SDCS from the two identically prepared samples of 5.8 and 7.8 ng/ml. Except for the FPIA, the SDC measured by the assays directly correlated with the amount of FAB in the sample, demonstrating the ability of these assays to measure free SDC.

Digoxin↗
PubMed1990

Effects of pentoxifylline and metabolite on red blood cell deformability as measured by ektacytometry.

The present investigation sought to evaluate the effects of pentoxifylline and its major hydroxyhexyl metabolite on red blood cell (RBC) deformability using the technique of ektacytometry. Red blood cells were harvested from normal volunteers (normal RBCs) and patients with sickle cell disease (abnormal RBCs) and incubated with varying concentrations of pentoxifylline and its major metabolite for varying time periods. The deformability of both treated and untreated RBCs from both patient groups was assessed by ektacytometric analysis. In contrast to the in vitro effects of pentoxifylline on whole-blood filterability, the present results demonstrated no effect of pentoxifylline or metabolite on RBC deformability at any concentration or incubation time period. Pentoxifylline does not enhance RBC deformability following acute in vitro incubation, and this suggests the need for further evaluation of the mechanism of action of this drug.

Anemia, Sickle Cell↗
PubMed1990

Characterization of dexamethasone binding in normal and uremic human serum.

The purpose of this study was to examine the extent and linearity of dexamethasone binding over a wide concentration range in normal and uremic serum. Tritiated dexamethasone was added to both untreated and charcoal-treated pooled normal serum and to pooled uremic serum to produce concentrations similar to those attained therapeutically (10-1000 ng/mL). Protein binding was determined by equilibrium dialysis at 37 degrees C. Dexamethasone serum binding was linear over the entire range of concentrations for each set of pooled serum. The mean (+/- SD) percent bound (mean +/- SD) for dexamethasone was similar for untreated (75.1 +/- 3.6 percent) and charcoal-treated (77.3 +/- 3.5 percent) normal serum. Dexamethasone binding (69.2 +/- 1.8 percent, p less than 0.05) and serum albumin concentrations (39.9 vs. 55.1 mmol/L) were significantly less in uremic vs. normal serum, respectively. These results suggest that (1) the binding of dexamethasone is linear and occurs primarily to albumin, with little or no binding to corticosteroid-binding globulin; (2) endogenous cortisol does not compete with dexamethasone for protein binding sites; and (3) steroid pharmacokinetics may be altered in uremic patients due to the 24 percent higher free fraction of dexamethasone in this population.

Adult↗
PubMed1990

Influence of pentoxifylline on steady-state theophylline serum concentrations from sustained-release formulations.

This clinical study assessed the influence of pentoxifylline and its metabolites on steady-state serum theophylline concentrations. Nine healthy volunteers took sustained-release formulations of pentoxifylline, theophylline, and a combination of both agents each for 7 days at standard therapeutic doses in a randomized order. Serum theophylline concentrations were analyzed using fluorescence-polarization immunoassay (TDx) technique. During the pentoxifylline treatment phase, serum theophylline concentrations were undetectable, demonstrating the lack of assay interference from pentoxifylline and its metabolites. Mean trough steady-state serum theophylline concentrations were 30% higher (p less than 0.05) during the combination treatment phase compared to theophylline administration alone, and varied considerably. Although side effects were more frequent during the combination phase, differences in the number of adverse reactions did not achieve statistical significance. This study demonstrates an interaction between theophylline and pentoxifylline, and indicates that close monitoring of serum theophylline concentrations during combination therapy is warranted.

Adolescent↗
PubMed1990

Antibiotics for common infections in the elderly.

A decline in host defense mechanisms and concurrent diseases combine to make the elderly patient particularly susceptible to common infections. The bacterial cause and antimicrobial sensitivity patterns may also be different in the elderly. The appropriate selection and dosing of antibiotics for elderly patients with such common infections as pneumonia, bronchitis, urinary tract infections, and skin and soft-tissue infections will optimize the patient's response while minimizing adverse consequences.

Age Factors↗
PubMed1989

The antihypertensive response to lisinopril: the effect of age in a predominantly black population.

After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.

Adult↗
PubMed1988

A framework for management of chronic pain.

The management of chronic pain requires a physician who is motivated to provide care for patients with this difficult problem. A thorough search must be made to determine the cause of the pain, the extent of psychiatric overlay, the importance of the pain to the patient (litigation, secondary gain), the extent of illness behavior and the response to previous therapy. The physician must be part of the treatment rather than part of the problem. Narcotic analgesics should be avoided except in patients with cancer pain or terminal illness.

Analgesia↗
PubMed1987

Exploring psychiatric prescribing practices: the relationship between the role of the provider and the appropriateness of prescribing.

The prescribing habits of psychiatrists and neurologists in a large, urban Veterans Administration medical center were surveyed. It was determined that these physicians prescribed a large amount of nonpsychotropic medication, and the rationale for this practice was explored and is presented. Patient expectations in this population derived from certain established sociocultural biases toward the medical profession appeared to significantly influence prescribing practices. Such prescribing behavior suggests that the psychiatrist in this setting is often required to assume the role of primary care provider as part of a larger patient therapist relationship.

Combined Modality Therapy↗
PubMed1986

Tailoring the antihypertensive drug regimen.

The challenge to the clinician is the need to choose among an array of antihypertensive agents in order to arrive at a regimen that is not only effective but also safe and convenient. Tailoring the regimen to the individual patient requires careful consideration of the pathophysiologic mechanisms that may be operative, concurrent risk factors and diseases, previous responses to other antihypertensive agents and the patient's general lifestyle, including diet and exercise.

Adrenal Glands↗